Skip to main content

Advertisement

SpringerLink
Log in

Measurement of glycated hemoglobin levels using an integrated microfluidic system

  • Research Paper
  • Published:
Microfluidics and Nanofluidics Aims and scope Submit manuscript

Abstract

Diabetes mellitus (DM) is a common non-communicable disease worldwide. Since DM may lead to serious complications, its treatment and care relies on early diagnosis leading to strict glycemic control monitored by the periodic measurement of the patients’ blood glucose levels. However, glucose levels can easily fluctuate due to diet, exercise, insulin resistance, stress, and other factors. Alternatively, the percentage of glycated hemoglobin (HbA1c) in the blood reflects an average glucose concentration over the past 2–3 months with fewer variations due to non-glycemic factors. Therefore, the accurate measurement of the HbA1c in the blood provides a more effective route to diagnose and to monitor DM than a conventional blood glucose measurement. For the measurement of HbA1c, immunoassays have become a widely used method. Therefore, to demonstrate automatic HbA1c measurement, we have developed a microfluidic system to perform a chemiluminescence immunoassay on a single chip automatically except the treatment of samples was undertaken off-chip and required centrifugation. Compared to routine clinical protocols, which rely on bulky benchtop instruments, the developed system is more compact in size (3.8-cm wide and 6.8-cm long) and consumes less samples (volume = 1 μL) and reagents (volume = 150 μL). It is also less labor-intensive to perform an immunoassay using this chip. With further refinements in assay development, this device may be a promising replacement for conventional HbA1c measurement in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

Bio-MEMS:

Bio-micro-electro-mechanical systems

CNC:

Computer numerical control

DI:

Deionized

DM:

Diabetes mellitus

ELISA:

Enzyme-linked immunosorbent assay

EMV:

Electromagnetic valve

Hb:

Hemoglobin

HbA1c:

Glycated hemoglobin

MEMS:

Micro-electro-mechanical systems

PBS:

Phosphate-buffered saline

PBST:

PBS with 1 % of surfactant Tween 20

PC:

Personal computer

PDMS:

Polydimethylsiloxane

PMMA:

Polymethylmethacrylate

PMT:

Photomultiplier tube

RLU:

Relative luminescence units

rpm:

Revolutions per minute

SA:

Streptavidin

μ-TAS:

Micro-total-analysis-system

References

  • Abraham EC, Perry RE, Stallings M (1983) Application of affinity chromatography for separation and quantitation of glycosylated hemoglobins. J Lab Clin Med 102(2):187–197

    Google Scholar 

  • American Diabetes Association (2013) Standards of medical care in diabetes. Diabetes Care 36:S11–S66

    Article  Google Scholar 

  • Choi JW, Oh KW, Thomas JH, Heineman WR, Halsall HB, Nevin JH, Helmicki AJ, Hendersona HT, Ahn CH (2002) An integrated microfluidic biochemical detection system for protein analysis with magnetic bead-based sampling capabilities. Lab Chip 2(1):27–30

    Article  Google Scholar 

  • Folch A, Ayon A, Hurtado O, Schmidt MA, Toner M (1999) Molding of deep polydimethylsiloxane microstructures for microfluidics and biological applications. J Biomech Eng 121(1):28–34

    Article  Google Scholar 

  • Huang CJ, Chien HC, Chou TC, Lee GB (2011) Integrated microfluidic system for electrochemical sensing of glycosylated hemoglobin. Microfluid Nanofluid 10(1):37–45

    Article  Google Scholar 

  • Huang CJ, Lin HI, Shiesh SC, Lee GB (2012) An integrated microfluidic system for rapid screening of alpha-fetoprotein specific aptamers. Biosens Bioelectron 35:50–55

    Article  Google Scholar 

  • John WG, Gray MR, Bates DL, Beacham JL (1993) Enzyme immunoassay—a new technique for estimating hemoglobin A1c. Clin Chem 39(4):663–666

    Google Scholar 

  • Kaufman FR, Gibson LC, Halvorson M, Carpenter S, Fisher LK, Pitukcheewanont P (2001) A pilot study of the continuous glucose monitoring system clinical decisions and glycemic control after its use in pediatric type 1 diabetic subjects. Diabetes Care 24(12):2030–2034

    Article  Google Scholar 

  • Lee WB, Chen YH, Lin HI, Shiesh SC, Lee GB (2011) An integrated microfluidic system for fast, automatic detection of C-reactive protein. Sens Actuators B Chem 157(2):710–721

    Article  Google Scholar 

  • Little RR, Roberts WL (2009) Laboratory advances in hemoglobin A1c measurement: a review of variant hemoglobins interfering with hemoglobin A1c measurement. J Diabetes Sci Technol (Online) 3(3):446–451

    Article  Google Scholar 

  • Little RR, Wiedmeyer HM, England JD, Wilke AL, Rohlfing CL, Wians FH, Goldstein DE (1992) Interlaboratory standardization of measurements of glycohemoglobins. Clin Chem 38(12):2472–2478

    Google Scholar 

  • Maluf N, Williams K (2004) Introduction to microelectromechanical systems engineering. Artech House Publishers, London

    Google Scholar 

  • Metus P, Ruzzante N, Bonvicini P, Meneghetti M, Zaninotto M, Plebani M (1999) Immunoturbidimetric assay of glycated hemoglobin. J Clin Lab Anal 13(1):5–8

    Article  Google Scholar 

  • Pecoraro RE, Graf RJ, Halter JB, Beiter H, Porte D (1979) Comparison of a colorimetric assay for glycosylated hemoglobin with ion-exchange chromatography. Diabetes 28(12):1120–1125

    Article  Google Scholar 

  • Pirart J (1977) Diabetes-mellitus and its degenerative complications—a prospective-study of 4,400 patients observed between 1947 and 1973. Diabetes Metab 3(2):97–107

    Google Scholar 

  • Rohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennill A, Goldstein DE (2002) Defining the relationship between plasma glucose and HbA1c analysis of glucose profiles and HbA1c in the Diabetes Control and Complications Trial. Diabetes Care 25(2):275–278

    Article  Google Scholar 

  • Saudek CD, Herman WH, Sacks DB, Bergenstal RM, Edelman D, Davidson MB (2008) A new look at screening and diagnosing diabetes mellitus. J Clin Endocr Metab 93(7):2447–2453

    Article  Google Scholar 

  • Stöllner D, Stöcklein W, Scheller F, Warsinke A (2002) Membrane-immobilized haptoglobin as affinity matrix for a hemoglobin-A1c immunosensor. Anal Chim Acta 470(2):111–119

    Article  Google Scholar 

  • UK Prospective Diabetes Study Group (1998) Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. Brit Med J 352:703–713

  • Weeks I, Beheshti I, McCapra F, Campbell AK, Woodhead JS (1983) Acridinium esters as high-specific-activity labels in immunoassay. Clin Chem 29(8):1474–1479

    Google Scholar 

  • Weng CH, Huang CJ, Lee GB (2012) Screening of aptamers on microfluidic systems for clinical applications. Sensors Basel 12(7):9514–9529

    Article  Google Scholar 

  • Yang YN, Lin HI, Wang JH, Shiesh SC, Lee GB (2009) An integrated microfluidic system for C-reactive protein measurement. Biosens Bioelectron 24(10):3091–3096

    Article  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the financial support provided to this study by the National Science Council in Taiwan (NSC102-2218-E-007-001). Partial financial support from the “Towards a World-Class University” Project is also greatly appreciated.

Author information

Authors and Affiliations

  1. Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, Taiwan

    Ching-Chu Wu, Ko-Wei Chang & Gwo-Bin Lee

  2. Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan

    Gwo-Bin Lee

  3. Institute of NanoEngineering and Microsystems, National Tsing Hua University, Hsinchu, 30013, Taiwan

    Gwo-Bin Lee

  4. Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University, Tainan, Taiwan

    Hsin-I Lin & Shu-Chu Shiesh

  5. Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong

    John D. Mai

Authors
  1. Ching-Chu Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hsin-I Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ko-Wei Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John D. Mai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shu-Chu Shiesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gwo-Bin Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Shu-Chu Shiesh or Gwo-Bin Lee.

Additional information

The preliminary results in this paper have been presented at the 17th International Conference on Miniaturized Systems for Chemistry and Life Sciences, µTAS 2013 Conference, Freiburg, Germany, October 27–31, 2013.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, CC., Lin, HI., Chang, KW. et al. Measurement of glycated hemoglobin levels using an integrated microfluidic system. Microfluid Nanofluid 18, 613–621 (2015). https://doi.org/10.1007/s10404-014-1460-5

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10404-014-1460-5

Keywords

Search

Navigation